Volume 29, Issue 161, July 2025

Psilocybin-assisted treatment of depression

Barbara Anna Zapalska^1♦, Antonina Teresa Witkowska², Anna Cukrowska³, Artur Galus⁴

¹Independent Public Central Clinical Hospital of University Clinical Centre of Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland
²Praga Hospital of the Transfiguration of the Lord, Aleja Solidarności 67, 03-401 Warsaw, Poland
³Independent Public Complex of Healthcare Facilities in Ostrów Mazowiecka, Duboisa 68, 07-300 Ostrów Mazowiecka, Poland
⁴St. Anne’s Trauma Hospital, Barska 16/20, 02-315 Warsaw, Poland

^♦Corresponding author
Barbara Anna Zapalska - Independent Public Central Clinical Hospital of University Clinical Centre of Medical University of Warsaw, Banacha 1A, 02-097 Warsaw, Poland

ABSTRACT

Depression, a common mental disorder, affects people at different stages of life. Classic antidepressant treatment is generally effective, however, it is prolonged. Nonetheless, numerous patients who undergo various classic antidepressant therapies still suffer from depression. Therefore, the search for novel medications is essential. In this review, we explore the therapeutic potential of psilocybin, an alkaloid found in several species of psilocybe mushrooms. Psilocybin mainly acts agonistically through serotonin 5-hydroxytryptamine type 2A (5-HT2A) receptors. However, the exact mechanism of the proposed antidepressant impact remains unknown. In the reviewed materials, psilocybin demonstrated rapid and longlasting antidepressant activity in treatment-resistant depression - the therapeutic effect occurred after only a single dose and was sustained for up to 12 weeks. The intensity of psychedelic experience correlated with the strength of the antidepressant action. In comparison to escitalopram, psilocybin acted more quickly and had longer-lasting effects, suggesting its potential as an alternative to classic antidepressants. The adverse events of psilocybin were mild. The findings presented in our work offer a promising perspective for patients who have previously not responded to standard antidepressant treatment.

Keywords: psilocybin, depression, depression treatment

Medical Science, 2025, 29, e110ms3657

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DOI: https://doi.org/10.54905/disssi.v29i161.e110ms3657

Published: 21 July 2025